Evaluation of three hollow-fiber membrane oxygenators without integrated arterial filters for neonatal cardiopulmonary bypass.

The cardiopulmonary bypass (CPB) procedure has been shown to be a possible cause of postoperative neurological morbidity for various reasons, including: large amounts of gaseous microemboli (GME) reaching the patient and hypoperfusion of the patient due to "stolen" blood flow. This study used a simulated CPB circuit identical to that in a clinical setting to examine three different hollow-fiber membrane oxygenators without intergrated arterial filters - the Capiox RX05, the Quadrox-i neonatal, and the KIDS D100 - to determine their ability to reduce the number of GME delivered to the neonatal patient and their hemodynamic properties in response to varying flow rates, normothermic vs hypothermic conditions, and open vs closed purge line. The circuit was primed with Ringer's Lactate and then human blood with a hematocrit of 30%. Injections of 5cc bolusses of air were injected into the venous line proximal to the venous reservoir over a thirty-second interval. Six injections were done for each oxygenator at each of the eight different experimental conditions for a total of 64 experiments per oxygenator (192 total injections). A flow probe, pressure transducer, and Emboli Detection and Classification (EDAC) quantifier transducer were positioned both upstream and downstream of the oxygenator to measure differences in each parameter. Results demonstrated that the Capiox RX05 is the most effective oxygenator at reducing the number of microemboli that potentially can be delivered to the neonatal patient. In regards to the hemodynamic properties, the Quadrox-i has the most favorable results, with the lowest mean pressure drop and the best energy retention across the oxygenator.

Evaluation of Quadrox-i and Capiox FX neonatal oxygenators with integrated arterial filters in eliminating gaseous microemboli and retaining hemodynamic properties during simulated cardiopulmonary bypass.

Perfusion quality during cardiopulmonary bypass (CPB) procedures can contribute to postoperative neurological complications and influence patient recovery and outcome. Gaseous microemboli generated in the circuit and hemodynamic properties of blood reaching the patient can be monitored during CPB to optimize perfusion. Oxygenators that oxygenate the blood during CPB can significantly influence the quality of blood reaching the patient by their manufacturing designs. New hollow-fiber membrane oxygenators are developed with integrated arterial filters to reduce priming volume and eliminate a separate arterial filter in the circuit. To evaluate the performance of these new oxygenators, we used a simulated model to compare the Quadrox-i Neonatal and the Capiox Baby FX05 neonatal oxygenators and to provide a review of these oxygenators with their respective counterparts which have separate arterial filters. We found that microemboli counts for the new Quadrox-i and Capiox FX05 oxygenators are similar in the arterial line, but different across the oxygenator for all experimental conditions. The arterial purge line diverting blood from the patient reduces microemboli count for the Capiox FX05, but is inconsistent for the Quadrox-i Neonatal. While hemodynamic energy delivered to the patient is similar for both oxygenators, shunted blood flow for the Quadrox-i Neonatal oxygenator is three times higher than the Capiox FX05 (103.6 mL/min vs 33.0 mL/min at 400 mL/min and 35°C) (p<0.001).

Evaluation of four pediatric cardiopulmonary bypass circuits in terms of perfusion quality and capturing gaseous microemboli.

This study compared four pediatric cardiopulmonary bypass (CPB) circuits with four different hollow-fiber membrane oxygenators and their specific reservoirs, Capiox RX15, Quadrox-i pediatric, Quadrox-i pediatric with integrated arterial filter (IAF) and KIDS D101, in a simulated CPB circuit identical to that used in the clinical setting at our institution to test their ability to maintain hemodynamic properties, remove gaseous microemboli (GME), and to test the amount of blood "stolen" by the arterial filter purge line. The circuit was first primed with Ringer's Lactate solution, then red blood cells were added and the hematocrit was maintained at 30%. A 5-cc bolus of air was injected just proximal to the venous reservoir over a thirty-second interval and GME were monitored using an Emboli Detection and Classification quantifier. Transducers were placed at pre-oxygenator, post-oxygenator and distal arterial line (post-filter) positions. Flow probes were also placed both pre and post filter. The injections were made at three flow rates, hypothermic and normothermic temperatures, and with the purge line in both the opened and closed positions. Six injections were done at each of the 12 experimental conditions. Results demonstrated that GME in the arterial line increased with increasing temperature and flow rate. The Capiox RX15 had the least GME in the arterial line at all experimental conditions. The KIDS D101 had the largest pressure drop and the lowest retention of hemodynamic energy, while the Capiox had the lowest pressure drop. All of the oxygenators had a similar amount of "stolen" blood flow and it was consistently under 10% of the total flow reaching the patient.

Dried-plasma transport using a novel matrix and collection system for human immunodeficiency virus and hepatitis C virus virologic testing.

A novel method for the collection and transportation of dried-blood-plasma samples, SampleTanker (ST), was developed and compared to standard shipping protocols for frozen-plasma specimens containing human immunodeficiency virus type 1 (HIV-1) and/or hepatitis C virus (HCV). Matched frozen and dried 1-ml EDTA-containing plasma samples were collected and analyzed by several molecular-based virologic assays. After addition of 1.175 ml of reconstitution buffer, 1.035 ml of dried plasma was recovered. Mean intra-assay variances were 0.05, 0.05, and 0.06 log(10) copies/ml for the Versant, Amplicor, and NucliSens QT HIV-1 load assays, respectively (P, not significant). However, mean HIV-1 viral load was consistently reduced in dried samples by 0.32 to 0.51 log(10) copies/ml, depending on assay type (P < 0.05). Infectious HIV-1 was not recovered from dried ST plasma. There was no significant difference in HIV-1 viral load results obtained using ST after 8 weeks of storage at ambient temperature. Compared to frozen plasma, HIV-1 genotypic results were >99% concordant at the nucleotide and amino acid levels, as well as for resistance-associated mutations. We further demonstrated successful detection of multiple analytes, including HIV-1 viral load, HIV-1 antiretroviral resistance genotype, and HCV genotype, from a single ST unit. Dried plasma collected with ST yielded comparable results to frozen samples for multiple-analyte clinical testing. As such, ST could be a useful alternative for virologic tests and clinical trials worldwide by significantly diminishing transportation cost and the sample volume restrictions associated with dried-blood-spot technology.

AMPK promotes tolerance to Ras pathway inhibition by activating autophagy.

Targeted inhibitors of oncogenic Ras (rat sarcoma viral oncogene)-Raf signaling have shown great promise in the clinic, but resistance remains a major challenge: 30% of tumors with pathway mutations do not respond to targeted inhibitors, and of the 70% that do respond, all eventually develop resistance. Before cancer cells acquire resistance, they respond to initial drug treatment either by undergoing apoptosis ('addiction') or by surviving treatment albeit with reduced growth ('tolerance'). As these drug-tolerant cells serve as a reservoir from which resistant cells eventually emerge, inhibiting the pathways that confer tolerance could potentially delay or even prevent recurrence. Here, we show that melanomas and other cancers acquire tolerance to Ras-Raf pathway inhibitors by activating autophagy, which is mediated by the cellular energy sensor AMP-activated protein kinase (AMPK). Blocking this AMPK-mediated autophagy sensitizes drug-tolerant melanomas to Ras-Raf pathway inhibitors. Conversely, activating AMPK signaling and autophagy enables melanomas that would otherwise be addicted to the Ras-Raf pathway to instead tolerate pathway inhibition. These findings identify a key mechanism of tolerance to Ras-Raf pathway inhibitors and suggest that blocking either AMPK or autophagy in combination with these targeted inhibitors could increase tumor regression and decrease the likelihood of eventual recurrence.

ATP concentration in Escherichia coli during oxygen toxicity.

Escherichia coli, strain E-26, grown in defined salts medium with glucose as the sole carbon and energy source, contained 1.50+/-0.16-10(6) molecules of ATP/cell. ATP was extracted with HC104 and assayed with a Dupont Luminescence Biometer using the luciferin-luciferase assay. Exposure during exponential growth at 37degreesC to 4.2 atm of oxygen resulted in complete growth cessation within 5 min, and to cyclic changes in cellular ATP concentration over a 2 h period. However, significant decrease in cellular ATP concentration occurred after growth inhibition in hyperbaric oxygen; hence, lack of ATP was not the cause of growth inhibition from oxygen toxicity.

[Glance at tropical dermatitis]. / Coup d'œil sur une dermatite tropicale.

We report a case of a French soldier, among more than fifteen others, who looked for dermatitis occurred in Central African Republic revealing a lepidopterism. We detail the Anaphae venata etiologic agent, what to do diagnosis and treatment.

The early nodulin gene MtN6 is a novel marker for events preceding infection of Medicago truncatula roots by Sinorhizobium meliloti.

MtN6 belongs to a series of cDNA clones representing Medicago truncatula genes transcriptionally activated during nodulation by Sinorhizobium meliloti (P. Gamas, F. de Carvalho Niebel, N. Lescure, and J. V. Cullimore, Mol. Plant-Microbe Interact. 9:233-242, 1996). We show here by in situ hybridization that MtN6 transcripts specifically accumulate first at very localized regions in the outer root cell layers, corresponding to outer cortical cells containing preinfection threads. At later stages, MtN6 expression is observed ahead of growing infection threads, including in the infection zone of mature root nodules. Interestingly, regulation of MtN6 is clearly distinct from that of other early nodulins expressed in the same region of the nodule, in terms of response to bacterial symbiotic mutants and to purified Nod factors. We thus suggest that MtN6 represents the first specific marker of a pathway involved in preparation to infection, which is at least partly controlled by Nod factors. Finally, we discuss the intriguing sequence homology shown by MtN6 to a protein from Emericella (Aspergillus) nidulans, FluG, that plays a key role in controlling the organogenesis of conidiophores (B. N. Lee and T. H. Adams, Genes Dev. 8:641-651, 1994).

Asymmetric synthesis and biological evaluation of beta-L-(2R,5S)- and alpha-L-(2R,5R)-1,3-oxathiolane-pyrimidine and -purine nucleosides as potential anti-HIV agents.

In order to study the structure-activity relationships of L-oxathiolanyl nucleosides as potential anti-HIV agents, a series of enantiomerically pure L-oxathiolanyl pyrimidine and purine nucleosides were synthesized and evaluated for anti-HIV-1 activity in human peripheral blood mononuclear (PBM) cells. The key intermediate 8 was synthesized starting from L-gulose via 1,6-thioanhydro-L-gulopyranose. The acetate 8 was condensed with thymine, 5-substituted uracils and cytosines, 6-chloropurine, and 6-chloro-2-fluoropurine to give pyrimidine and purine nucleosides. Upon evaluation of these final nucleosides, the 5-fluorocytosine derivative 51 was found to be the most potent compound among those tested. In the case of 5-substituted cytosine analogues, the antiviral potency was found to be in the following decreasing order: cytosine (beta-isomer) > 5-iodocytosine (beta-isomer) > 5-fluorocytosine (alpha-isomer) > 5-methylcytosine (alpha-isomer) > 5-methylcytosine (beta-isomer) > 5-bromocytosine (beta-isomer) > 5-chlorocytosine (beta-isomer). Among the thymine, uracil, and 5-substituted uracil derivatives, thymine (alpha-isomer) and uracil (beta-isomer) derivatives exhibited moderate anti-HIV activity. In the purine series, the antiviral potency is found to be in the following decreasing order: adenine (beta-isomer) > 6-chloropurine (beta-isomer) > 6-chloropurine (alpha-isomer) > 2-NH2-6-Cl-purine (beta-isomer) > guanine (beta-isomer) > N6-methyladenine (alpha-isomer) > N6-methyladenine (beta-isomer). The cytotoxicity was also determined in human PBM cells as well as Vero cells. None of the synthesized nucleosides was toxic up to 100 microM in PBM cells.

Chronic nonspecific diarrhea: dietary relationships.

Chronic nonspecific diarrhea (CNSD) is the most common cause of prolonged diarrhea without failure to thrive. Although it is most commonly seen from ages 6 to 36 months, CNSD may persist until 54 months of age. Forty-four patients with this syndrome had complete dietary histories, and were divided into four groups on the basis of their intakes and responses to its modification. Each of the four groups had significantly less fat in their diet at the time of presentation than did ten non-CNSD patients (P less than .005) presenting similarly. In three of the groups, daily fat consumption was increased, irrespective of the adequacy of their initial intakes. In all 38 patients in these groups, this dietary modification was associated with the resolution of symptoms. The fourth group, with initially normal dietary fat ingestion, did not respond to dietary therapy. The overall success rate of the regimen in this patient population was 82%. Carbohydrate, fiber, and caloric contents of the diets did not appear to play as significant a role as fat intake.

DeSanctis-Cacchione syndrome. A case report with autopsy findings.

One of the first patients studied by Cleaver on the DNA repair defect to ultraviolet light damage in xeroderma pigmentosum has been subjected to autopsy examination. This patient had the DeSanctis-Cacchione syndrome (microcephaly, dwarfism, mental deficiency, and choreoathetosis). Her autopsy findings were similar to those of the other three patients with this syndrome, emphasizing olivopontocerebellar atrophy, who underwent autopsy. The patient apparently could not tolerate psoralens because of increased incidence of carcinoma formation.

Hepatomegaly. An approach to differential diagnosis.

Hepatomegaly is not an uncommon occurrence in infancy and childhood. When the pediatrician encounters a patient with an enlarged liver, he must carefully evaluate that patient in order to determine the necessary approach to establishing a diagnosis. Specific emphasis must be made as to those conditions which necessitate hospital admission and complete evaluation and those self-limited conditions which may resolve with time.

Properties of a glass-ionomer/resin-composite hybrid material.

A small percentage of the liquid resin used in commercial dental composites was added to the liquid used in a commercial glass-ionomer restorative in order to produce a fluoride-containing hybrid restorative-type material that would adhere to dentin while being stronger, less brittle, and less sensitive to desiccation in the oral cavity than glass ionomer. Compressive strength, yield strength, elastic modulus, fracture toughness, and tensile strength were analyzed for this hybrid, light-cured material. In addition, the solubility in water, adhesion to dentin, and surface roughness were also examined in vitro. The results suggest that the early (one-hour) mechanical properties of the hybrid material exceed those of glass ionomer. In addition, the brittleness and solubility of the material are less than those of commercial glass ionomer, while adhesion to dentin is unaffected. Most importantly, surface crazing, a documented problem with some glass ionomers when they become desiccated, is alleviated with this hybrid formulation.

Bilateral shoulder dislocation: an unusual occurrence.

Bilateral shoulder dislocation is an unusual clinical entity. Proposed mechanisms are via various traumatic insults, atraumatic occurrences, and through extreme muscular contractions. A case involving traumatic dislocation as a result of a diving incident is reported. A brief review of this rare clinical condition is presented.

Subacute acetaminophen overdose after incremental dosing.

A case of acetaminophen poisoning following the ingestion of 26 g of acetaminophen by incremental dosing over a 25-h period is reported. At presentation, seven h after the last ingestion, the patient experienced hematemesis, the acetaminophen level was 150 micrograms/mL, and the SGOT was normal. The patient recovered uneventfully following N-acetylcysteine therapy. A review of the pharmacology and toxicity of acetaminophen is discussed. The case illustrates the problems of judging hepatotoxic potential in a multiple-dose acetaminophen ingestion and describes the successful use of N-acetylcysteine in a patient with a "subacute" acetaminophen overdose.

Turbinate destruction--a rare complication of nasotracheal intubation.

Nasotracheal intubation is a procedure used in the emergency department for airway management. Although the procedure has its attendant complications, we report the rare occurrence of an inferior turbinectomy. Other complications of the procedure are discussed.

Isolation and metabolism cage system for newborn pigs.

An isolation system was designed and constructed for isolating normal and infected newborn pigs. The system consisted of an outer cage fitted with a biological diffusion filter and a dunk bath entry system and an inner metabolism cage to contain the pig. When tested with S-13 bacteriophage, the isolation and metabolism cage system was at least 99% efficient in preventing the entry or escape of microorganism. A total of 267 Escherichia coli-infected newborn pigs have been isolated in these units, with no cross contaminations.

Clinical estimation of liver size in the normal neonate.

Clinical estimates of liver size and comparative analysis of the clinical techniques of estimating liver size are not available for neonates. Liver span was determined by a pediatrician and pediatric nurse practitioner, in 100 consecutive normal term neonates at 1 and 3 days of life, using four methods. The most reproducible method in estimating liver size in neonates is either (1) percussion of the upper and lower borders of (2) percussion of the upper border and palpation of the lower border. The clinical estimate of liver size in a healthy term neonate is 5.65 cm, with a 95% confidence limit of 4.25 to 7.00 cm. These values provide a basis for comparison during routine examination.

Craniofacial characteristics of cyclopia in man and swine. Implications on role of medial structures in normal growth and development.

A rare and bizarre congenital deformity sheds light on the essential function of the nasal septum and other medial structures of cartilaginous origin in the vertical growth of the mid-face.

[Steinert disease and pregnancy]. / Maladie de Steinert et grossesse.

Steinert's syndrome and pregnancy with delivery are rarely associated. It is a dominant autosome disease. Certain signs in pregnancy may suggest that the fetus is affected. One case made it possible to demonstrate these facts. Hydramnios with infrequent fetal movements and a slow fetal heart rate may lead to a suspicion of fetal involvement. This is always serious. The presence of the disease in the mother should be sought if it is not already known. If there is already a known family history the patient should see a geneticist so long as early amniocentesis has not yet been performed.